Infection, Inflammation and Preeclampsia

描述(申请人提供)：先兆子痫是一种人类妊娠疾病，会导致相当大的孕产妇和围产期发病率。内皮损伤和功能障碍被认为发生在疾病过程的早期，可能与过度的血管内母体炎症反应有关。已知的是，与细胞因子产生上调相关的原发感染和基因多态可触发这种炎症反应。此外，感染剂和细胞因子可能通过诱导母体炎症介质和生长因子来激活内皮细胞。我们建议并行病例对照调查，嵌套在合作围产期项目(n=55,908)和丹麦国家出生队列(n=101,046)中。利用储存的产前首诊和产后血清标本，我们建议：1)确定母亲初次感染单纯疱疹病毒(HSV)-1、HSV-2、巨细胞病毒(CMV)、肺炎衣原体(CP)与子痫前期风险的关系；2)检查早孕细胞因子、CRP与子痫前期的关系；3)调查影响感染状态的多种因素及其与子痫前期的关系；4)调查细胞因子簇并确定其与子痫前期的关系。感染和炎症可能引发先兆子痫的概念将为了解这种疾病的病理生理学提供了洞察力。此外，它将建议采取公共卫生措施，如在育龄妇女中普遍进行HSV和CP筛查、治疗和接种疫苗，或在高危妇女中使用阿司匹林和抗氧化剂治疗。最后，细胞因子和C反应蛋白检测可能被证明是确定有患先兆子痫风险的妇女的有效工具。

DESCRIPTION (provided by applicant): Preeclampsia is a disease of human pregnancy that causes considerable maternal and perinatal morbidity. Endothelial injury and dysfunction are thought to occur early in the disease process, and may relate to an excessive intravascular maternal inflammatory response. Primary infections and polymorphisms associated with upregulated cytokine production are known to trigger such an inflammatory response. Furthermore, infectious agents and cytokines may invoke endothelial activation through induction of maternal inflammatory mediators and growth factors. We propose parallel case-control investigations, nested within the Collaborative Perinatal Project (n = 55,908) and the Danish National Birth Cohort (n = 101,046). Using stored first prenatal visit and postnatal serum samples, we propose to: 1) determine the relationship between maternal primary infection with Herpes Simplex Virus (HSV)-1, HSV-2, Cytomegalovirus (CMV), Chlamydia Pneumoniae (CP) and the risk of preeclampsia; 2) examine the relationship between early pregnancy cytokines, CRP and preeclampsia; 3) investigate multiple factors affecting infection status and its relation to preeclampsia; and 4) investigate cytokine clusters and determine their associations with preeclampsia. The notion that infection and inflammation may trigger preeclampsia would provide insight into the pathophysiology of this condition. Further, it would suggest public health measures, such as universal HSV and CP screening, treatment, and vaccination among women of reproductive age, or aspirin and antioxidant therapy among high risk women. Finally, cytokine and CRP testing may prove to be effective tools for identifying women at risk for developing preeclampsia.